Laser assisted pharmaceutical delivery and fluid removal

Abstract

The present invention provides an improved method of removing fluids, gases or other biomolecules, or delivering a pharmaceutical composition, through the skin of a patient without the use of a sharp or needle. The method includes the step of irradiating the stratum corneum, an applied pharmaceutical or an absorbing material, using a laser. By selection of parameters, the laser irradiates the selected material or tissue to create pressure gradients, plasma, cavitation bubbles, or other forms of tissue ablation or alteration. These methods increase the diffusion of pharmaceuticals into, or fluids, gases or other biomolecules out of, the body. For this invention, a pharmaceutical composition can be applied to the skin before or after laser irradiation.

We claim:  
     
       1. A method for preparing the skin for treatment of cutaneous or subcutaneous compounds, comprising the steps of: 
       a) focusing a laser beam with sufficient energy fluence to alter the skin at least as deep as the stratum corneum, but not as deep as the capillary layer;  
       b) firing the laser to create a site of alteration, the site having a diameter of between 0.5 microns and 5.0 cm;  
       c) applying a dye, a compound that alters the optical properties of stratum corneum, or a compound that stimulates the body's production of molecules that are strong absorbers of light; and  
       d) firing a second laser with a wavelength that is absorbed by the applied dye, the compound that stimulates the optical properties of stratum corneum or the compound that stimulates the body's production of molecules that are strong absorbers of light.  
     
     
       2. The method of claim  1  wherein the laser beam has a wavelength of 0.2-10 microns. 
     
     
       3. The method of claim  1  wherein the laser beam has a wavelength of between 1.5-3.0 microns. 
     
     
       4. The method of claim  1  wherein the laser beam has a wavelength of about 2.94 microns. 
     
     
       5. The method of claim  1  wherein the laser beam is emitted by a laser selected from the group consisting of continuous wave-lasers Er:YAG, pulsed CO 2 , Ho:YAG, Er:YAP, Er/Cr:YSGG, Ho:YSGG, Er:GGSG, Er:YLF, Tm:YAG, Ho:YAG, Ho/Nd:Yalo 3 , cobalt:MgF 2 , HF chemical, DF chemical, carbon monoxide, deep UV lasers, and frequency tripled Nd:YAG lasers. 
     
     
       6. The method of claim  1  wherein the laser beam is emitted by a modulated laser selected from the group consisting of continuous-wave CO 2 , Nd:YAG, Thullium:YAG and diode lasers. 
     
     
       7. The method of claim  1  wherein the laser beam is emitted by an Er:YAG laser. 
     
     
       8. The method of claim  1  wherein the laser beam is focused at a site on the skin with a diameter of 0.1-5.0 mm. 
     
     
       9. The method of claim  1  wherein the energy fluence of the laser beam at the skin is 0.03-100,000 J/cm 2 . 
     
     
       10. The method of claim  1  wherein the energy fluence of the laser beam at the skin is 0.03-9.6 J/cm 2 . 
     
     
       11. The method of claim  1  wherein the pulse width is between 1 femtosecond and 1,000 microseconds. 
     
     
       12. The method of claim  1  wherein the pulse width is between 1 and 1000 microseconds. 
     
     
       13. The method of claim  1  wherein multiple alterations are made to prepare the skin for dye delivery. 
     
     
       14. The method of claim  1  further comprising a beam splitter positioned to create, simultaneously from the laser, multiple sites of alteration. 
     
     
       15. The method of claim  14  wherein the beam splitter is selected from a series of partially silvered mirrors, a series of dichroic mirrors, and a series of beam-splitting prisms. 
     
     
       16. The method of claim  14  further comprising a means to deflect the beam at different angles to create different sites of alteration on the skin. 
     
     
       17. The method of claim  14  further comprising a means to scan the laser beam to create one continuous path of alteration. 
     
     
       18. The method of claim  1  wherein the dye is used to stain subcutaneous structures. 
     
     
       19. The method of claim  1  wherein the dye is indocyanine green. 
     
     
       20. The method of claim  1  wherein the dye is specific for lipids, proteins, or carbohydrates. 
     
     
       21. The method of claim  1  wherein the wavelength of the laser beam fired from the second laser at the site of dye delivery is about the wavelength of peak absorption of the dye. 
     
     
       22. The method of claim  21  wherein the wavelength of the laser beam is about 810 nm. 
     
     
       23. The method of claim  1  wherein the wavelength of the laser beam fired from the second laser at the site of delivery of the compound that stimulates the body's production of molecules that are strong absorbers of light is about the wavelength of peak absorption of the compound. 
     
     
       24. The method of claim  23  wherein the compound that stimulates the body's production of molecules that are strong absorbers of light is 5-aminolevulinic acid. 
     
     
       25. A method for increasing the diffusion of bodily fluids out of, or compounds into, the skin, comprising the steps of: 
       a) applying a compound or an absorbing material to a targeted tissue site;  
       b) focusing a laser beam with sufficient energy fluence to create a pressure gradient within the stratum corneum, in the applied compound, or in the optional absorbing material; and  
       c) firing the laser with at least one short rapid pulse to create the pressure gradient.  
     
     
       26. The method of claim  25  wherein the laser beam has a wavelength of 0.2-10 microns. 
     
     
       27. The method of claim  25  wherein the laser beam has a wavelength of between 1.5-3.0 microns. 
     
     
       28. The method of claim  25  wherein the laser beam has a wavelength of about 2.94 microns. 
     
     
       29. The method of claim  25  wherein the laser beam is emitted by a laser selected from the group consisting of Er:YAG, pulsed CO 2  Ho:YAG, Er:YAP, Er/Cr:YSGG, Ho:YSGG, Er:GGSG, Er:YLF, Tm:YAG, Ho:YAG, Ho/Nd:YalO 3 , cobalt:MgF 2 , HF chemical, DF chemical, carbon monoxide, deep UV lasers, and frequency tripled Nd:YAG lasers. 
     
     
       30. The method of claim  25  wherein the laser beam is emitted by an Er:YAG laser. 
     
     
       31. The method of claim  25  wherein the laser beam is emitted by a modulated laser selected from the group consisting of continuous-wave CO 2 , Nd:YAG, Thallium:YAG and diode lasers. 
     
     
       32. The method of claim  25  wherein the pulse width is between 1 femtosecond and 1,000 microseconds. 
     
     
       33. The method of claim  25  wherein the pulse width is between 1 and 1000 microseconds. 
     
     
       34. The method of claim  25  wherein the optional absorbing material is placed on or over the targeted tissue before application of the compound or firing the laser. 
     
     
       35. The method of claim  34  wherein the pressure gradient is created in the optional absorbing material. 
     
     
       36. The method of claim  34  wherein the optional absorbing material is a thin film of water. 
     
     
       37. The method of claim  34  wherein the optional absorbing material is a dye or a solution with a dye. 
     
     
       38. The method of claim  25  wherein the compound is applied before firing the laser. 
     
     
       39. The method of claim  25  wherein the pressure gradient is created in the stratum corneum simultaneous with the application of the compound. 
     
     
       40. The method of claim  38  wherein the pressure gradient is created in the compound. 
     
     
       41. The method of claim  38  wherein the optional absorbing material is placed on or over the compound before firing the laser. 
     
     
       42. The method of claim  41  wherein the pre ssure gradient is created in the optional absorbing material. 
     
     
       43. The method of claim  41  wherein the optional absorbing material is a thin film of water. 
     
     
       44. The method of claim  25  wherein multiple pulses are used to create the pressure gradient. 
     
     
       45. The method of claim  25  wherein the stratum corneum is ablated or altered before the pressure gradient is created. 
     
     
       46. A method for increasing the diffusion of bodily fluids out of, or compounds into, the skin, comprising the steps of: 
       a) focusing a laser beam with sufficient energy fluence to create plasma in an optional absorbing material on or over a targeted tissue site;  
       b) firing the laser with at least one short rapid pulse to create a site of plasma, the site having a diameter of between 0.5 microns and 5 mm; and  
       c) removing bodily fluids from the targeted tissue or applying a compound to the targeted tissue.  
     
     
       47. The method of claim  46  wherein the laser beam has a wavelength of 0.2-10 microns. 
     
     
       48. The method of claim  46  wherein the laser beam has a wavelength of between 1.5-3.0 microns. 
     
     
       49. The method of claim  46  wherein the laser beam has a wavelength of about 2.94 microns. 
     
     
       50. The method of claim  46  wherein the laser beam is emitted by a laser selected from the group consisting of Er:YAG, pulsed CO 2  Ho:YAG, Er:YAP, Er/Cr:YSGG, Ho:YSGG, Er:GGSG, Er:YLF, Tm:YAG, Ho:YAG, Ho/Nd:YalO 3 , cobalt:MgF 2 , HF chemical, DF chemical, carbon monoxide, deep UV lasers, and frequency tripled Nd:YAG lasers. 
     
     
       51. The method of claim  46  wherein the laser beam is emitted by an Er:YAG laser. 
     
     
       52. The method of claim  46  wherein the laser beam is emitted by a modulated laser selected from the group consisting of continuous-wave CO 2 , Nd:YAG, Thallium:YAG and diode lasers. 
     
     
       53. The method of claim  46  wherein the pulse width is between 1 femtosecond and 1,000 microseconds. 
     
     
       54. The method of claim  46  wherein the pulse width is between 1 and 1000 microseconds. 
     
     
       55. The method of claim  46  wherein multiple pulses are used to create multiple sites of plasma. 
     
     
       56. The method of claim  46  wherein the optional absorbing material is placed on or over the targeted tissue before firing the laser. 
     
     
       57. The method of claim  56 , wherein plasma is created in the optional absorbing material. 
     
     
       58. The method of claim  56 , wherein the optional absorbing material is a thin film of water. 
     
     
       59. The method of claim  56 , wherein the optional absorbing material is a dye or a solution with a dye. 
     
     
       60. The method of claim  46  wherein the compound is applied before firing the laser. 
     
     
       61. The method of claim  60 , wherein plasma is created in the applied compound. 
     
     
       62. A method for increasing the diffusion of bodily fluids out of, or compounds into, the skin, comprising the steps of: 
       a) focusing a laser beam with sufficient energy fluence to create cavitation bubbles in an applied compound, or in an optional absorbing material on or over a targeted tissue site;  
       b) firing the laser with at least one short rapid pulse to create a site of cavitation bubbles, the site having a diameter of between 0.5 microns and 5 mm; and  
       c) removing bodily fluids from the targeted tissue or applying a compound to the targeted tissue.  
     
     
       63. The method of claim  62 , wherein the laser beam has a wavelength of 0.2-10 microns. 
     
     
       64. The method of claim  62 , wherein the laser beam has a wavelength of between 1.5-3.0 microns. 
     
     
       65. The method of claim  62 , wherein the laser beam has a wavelength of about 2.94 microns. 
     
     
       66. The method of claim  62 , wherein the laser beam is emitted by a laser selected from the group consisting of Er:YAG, pulsed CO 2  Ho:YAG, Er:YAP, Er/Cr:YSGG, Ho:YSGG, Er:GGSG, Er:YLF, Tm:YAG, Ho:YAG, Ho/Nd:YalO 3 , cobalt:MgF 2 , HF chemical, DF chemical, carbon monoxide, deep UV lasers, and frequency tripled Nd:YAG lasers. 
     
     
       67. The method of claim  62 , wherein the laser beam is emitted by an Er:YAG laser. 
     
     
       68. The method of claim  62 , wherein the pulse width is between 1 femtosecond and 1,000 microseconds. 
     
     
       69. The method of claim  62 , wherein the pulse width is between 1 and 1000 microseconds. 
     
     
       70. The method of claim  62 , wherein the laser beam is emitted by a modulated laser selected from the group consisting of continuous-wave CO 2 , Nd:YAG, Thallium:YAG and diode lasers. 
     
     
       71. The method of claim  62 , wherein multiple pulses are used to create multiple sites of cavitation bubbles. 
     
     
       72. The method of claim  62 , wherein the optional absorbing material is placed on or over the targeted tissue before firing the laser. 
     
     
       73. The method of claim  72 , wherein the cavitation bubbles are created in the optional absorbing material. 
     
     
       74. The method of claim  72 , wherein the optional absorbing material is a thin film of water. 
     
     
       75. The method of claim  72 , wherein the optional absorbing material is a dye or a solution with a dye. 
     
     
       76. The method of claim  62 , wherein the compound is applied before firing the laser. 
     
     
       77. The method of claim  76 , wherein the cavitation bubbles are created in the applied compound.